The purpose of this project is to define the biochemical interactions of biodegradable organophosphorus insecticides with vital non-cholinergic macromolecules. Work performed during the preceding project period has focused on the fate of the reactive sulfur atoms produced during the desulfuration of parathion. The rapid analysis of phosphorus and metabolites by thin-layer chromatography and the technique of hepatocyte isolation have also been worked out. These studies form the basis for the next phase of research which includes the following objectives: 1. In vitro analysis of the effect of organophosphates on beta-glucuronidase release from hepatocytes; 2. Intralobular heterogeneity of mixed-function oxidases; 3. Significance of phosphorylation, hydrolysis and oxidation in the disposition of paraoxon. The data should ultimately yield the identity of the causal link between the formation of organophosphate-biomacromolecular covalent bonds and the untoward effects of these widely-used chemicals. The significance of this research lies in the enhancement of our ability to predict health hazards associated with organophosphorus insecticides and related chemicals.